Randomized, double-blind, placebo-controlled clinical trial of choline supplementation in school-aged children with fetal alcohol spectrum disorders

Abstract

Background: Prenatal alcohol exposure results in a broad range of cognitive and behavioral impairments. Because of the long-lasting problems that are associated with fetal alcohol spectrum disorders (FASDs), the development of effective treatment programs is critical. Preclinical animal studies have shown that choline, which is an essential nutrient, can attenuate the severity of alcohol-related cognitive impairments. Objective: We aimed to translate preclinical findings to a clinical population to investigate whether choline supplementation can ameliorate the severity of memory, executive function, and attention deficits in children with FASDs. Design: In the current study, which was a randomized, doubleblind, placebo-controlled clinical trial, we explored the effectiveness of a choline intervention for children with FASDs who were aged 5-10 y. Fifty-five children with confirmed histories of heavy prenatal alcohol exposure were randomly assigned to either the choline (n = 29) or placebo (n = 26) treatment arms. Participants in the choline group received 625 mg choline/d for 6 wk, whereas subjects in the placebo group received an equivalent dose of an inactive placebo treatment. Primary outcomes, including the performance on neuropsychological measures of memory, executive function, and attention and hyperactivity, were assessed at baseline and postintervention. Results: Compared with the placebo group, participants in the choline group did not differentially improve in cognitive performance in any domain. Treatment compliance and mean dietary choline intake were not predictive of treatment outcomes. Conclusions: Findings of the current study do not support that choline, administered at a dose of 625 mg/d for 6 wk, is an effective intervention for school-aged (5-10 y old) children with FASDs. This research provides important information about choline's therapeutic window. Combined with other studies of choline and nutritional interventions in this population, this study emphasizes a further need for the continued study of the role of nutritional status and supplementation in children with FASDs and the contributions of nutrition to neurocognition. This trial was registered at clinicaltrials.gov as NCT01911299.Am J Clin Nutr 2016;104:1683-92.

Effect of Choline Supplementation on Neurological, Cognitive, and Behavioral Outcomes in Offspring Arising from Alcohol Exposure During Development: A Quantitative Systematic Review of Clinical and Preclinical Studies

“…There were adequate data from all studies for quantitative comparison of the control and intervention groups for each outcome. However, there were no nonexposed control subjects included in the studies by Nguyen and colleagues () or Wozniak and colleagues () and so the effect of alcohol alone on the measured outcomes could not be evaluated.…”

“…For Nguyen and colleagues (), heavy prenatal alcohol exposure was determined via retrospective review of medical, social services, or adoption records and was defined as ≥4 drinks/occasion ≥1 time/wk or ≥14 drinks/wk during pregnancy. In the study reported by Wozniak and colleagues (), FASD was diagnosed using the modified Institute of Medicine (IOM) criteria (Hoyme et al., ) and the Centers for Disease Control and Prevention (CDC) criteria for FASD (Bertrand et al., ).…”

“…All participants were recruited from specialist clinics or postings on websites and Listservs for families of children with FASD. The clinics were located in Ohio and San Diego, USA (Nguyen et al., ); Minnesota, USA (Wozniak et al., ); and Western Ukraine (Coles et al., ; Kable et al., ). For Nguyen and colleagues (), 81 to 93% of the children were adopted.…”

“…The clinics were located in Ohio and San Diego, USA (Nguyen et al., ); Minnesota, USA (Wozniak et al., ); and Western Ukraine (Coles et al., ; Kable et al., ). For Nguyen and colleagues (), 81 to 93% of the children were adopted. Similarly, 1 of the clinics used for recruitment in Wozniak and colleagues () was an international adoption clinic, although the percentage of adopted children included was not reported.…”

The causal web of foetal alcohol spectrum disorders: a review and causal diagram

“…Nutritional supplementation has been found to attenuate FASD symptomology in some animal models [98]. Results in human studies are limited and inconsistent [113][114][115].…”